Heart failure (HF) is the fastest growing cardiovascular disorder in the U.S., and the most common reason for hospitalization among older adults. Many patients with HF have symptoms at rest or with minimal exertion that become refractory to optimal medical therapy. Fewer than 5% of these advanced HF patients are eligible for heart transplantation, and organ donations are extremely limited. As such, mechanical circulatory support with a ventricular assist device (VAD) has emerged as a primary treatment for advanced HF. There is significant and unexplained heterogeneity in clinical outcomes and quality-of-life after VAD implantation. Moreover, we know very little about how physical and psychological symptoms may relate to changes in underlying HF pathogenesis and how symptoms and pathogenic biomarkers may explain differential responses to VAD implantation. Accordingly, our research goals are to a) characterize common and distinct trajectories of change in symptoms and pathogenic biomarkers during the transition from advanced HF through the first 6 months after VAD implantation, and b) link changes in symptoms and biomarkers over time to clinical events and quality-of-life. We will collect data from a cohort of 120 adults with advanced HF prior to, and for a period of 6 months after VAD implantation. Our aims are to: 1) identify common trajectories of change in physical and psychological symptoms, 2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction, and 3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Importantly, we will codify the clinical relevance of different symptom and biomarker trajectories in terms of clinical-event risk and health-related quality-of-life. This interdisciplinary clinical research integrates and advances prior biological and behavioral research and is centered on an advanced technological treatment of a high profile cardiovascular disorder. These research findings will be used to enhance shared patient and provider decision-making regarding VAD implantation, and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation. PUBLIC HEALTH RELEVANCE: This study involves a primary treatment for advanced heart failure, the fastest growing cardiovascular disorder in the United States. The results of this stud will be used to enhance patient and provider decision-making about advanced therapies for heart failure, and to develop personalized interventions to improve patient- oriented and clinical outcomes.